Abstract 398: Tocomin Restores Endothelium-Dependent Relaxation in Diabetic Rat Aorta

Abstract

Increased superoxide in blood vessels can lead to impaired endothelial function. Tocotrienols, components of vitamin E are effective antioxidants that may have beneficial effects on vascular function particularly in pathologies involving oxidative stress such as diabetes. Tocomin is an extract of palm oil with high tocotrienol content. This study investigated the effect of 4 week treatment with tocomin (composition: tocotrienol rich fraction: 40%, α-tocopherol: 11% and palm olein: 38%) treatment on endothelium-dependent and endothelium-independent relaxation in the diabetic rat aorta. Male Wistar rats were randomly assigned to 4 groups (control, control+tocomin, diabetic and diabetic+tocomin). Diabetes was induced by a single injection of streptozotocin (STZ, 50 mg/kg iv). Rats were treated with tocomin (40 mg/kg per day s.c.) or vehicle (100% peanut oil) for 4 weeks commencing 6 weeks after induction of diabetes. Endothelium-dependent (EDR) to ACh, endothelium-independent relaxation (EIR) to sodium nitroprusside and superoxide production were measured using standard organ bath techniques and lucigenin enhanced chemiluminescence. Diabetes increased blood glucose (control 6.8±0.3 vs diabetic 32.1±1.2 mmol/L, n=7-9) and glycated hemoglobin (HbA1c control 5.6±0.2% vs diabetic 13.3±0.3%, n=7-9). Neither parameter was affected by tocomin treatment (blood glucose control+tocomin 7.3±0.7 mmol/L, diabetic+tocomin 26.3±4 mmol/L, HbA1c control+tocomin 5.5±0.2%, diabetic+tocomin 11.8±1.3%, n=8-10). Diabetes impaired EDR (ACh Rmax control 93±4% vs diabetic 76±4%, n=6-8, p<0.05) without affecting EIR. Tocomin treatment significantly improved EDR (ACh Rmax diabetic 76±4% vs diabetic+tocomin 89±3%, n=6-8, p<0.05) in diabetic rat aortae. Diabetes also significantly increased superoxide production (control 573±75 vs diabetic 1113±90 counts/mg dry tissue, n=4-9, p<0.05), which was alleviated by tocomin treatment (761±71 counts/mg dry tissue, n=4-9, p<0.05, in comparison to diabetic). These findings demonstrate that 4 week treatment of diabetic rats with tocotrienol rich tocomin significantly reduces superoxide production and improves EDR without affecting blood glucose levels.